OBJECTIVE: To demonstrate that the development of progressive osteopenia in ovariectomized rhesus monkeys can be prevented by treatment with the potent bisphosphonate zoledronate. RESULTS Ovariectomy produced rapid bone loss of ~8% at the lumbar spine and total body. This was prevented in a dose-dependent fashion by zoledronate. This study was the most comprehensive assessment of estrogen depletion bone loss and the effect of a bisphosphonate compound on this loss in the rhesus monkey. Elevated skeletal turnover was clearly demonstrated and was suppressed dose dependently by zoledronate. These results suggest that this compound will likely prove efficacious in the prevention and treatment of osteoporosis in postmenopausal women. FUTURE DIRECTIONS Quantitative histomorphometric assessment and biomechanical strength testing of samples from this study are pending. KEY WORDS Osteoporosis, bisphosphonate, estrogen-depletion, bone density, bone strength